Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus Erythematosus

被引：323

作者：

Yang, Wanling ^{[1
]}

Shen, Nan ^{[2
,3
,4
]}

Ye, Dong-Qing ^{[5
]}

Liu, Qiji ^{[1
,6
,7
]}

Zhang, Yan ^{[1
]}

Qian, Xiao-Xia ^{[2
,3
,4
]}

Hirankarn, Nattiya ^{[8
]}

Ying, Dingge ^{[1
]}

Pan, Hai-Feng ^{[5
]}

Mok, Chi Chiu ^{[9
]}

Chan, Tak Mao ^{[10
]}

Wong, Raymond Woon Sing ^{[10
]}

Lee, Ka Wing ^{[11
]}

Mok, Mo Yin ^{[10
]}

Wong, Sik Nin ^{[12
]}

Leung, Alexander Moon Ho ^{[13
]}

Li, Xiang-Pei ^{[14
]}

Avihingsanon, Yingyos ^{[15
]}

Wong, Chun-Ming ^{[16
]}

Lee, Tsz Leung ^{[1
]}

Ho, Marco Hok Kung ^{[1
]}

Lee, Pamela Pui Wah ^{[1
]}

Chang, Yuk Kwan ^{[1
]}

Li, Philip H. ^{[1
]}

Li, Ruo-Jie ^{[1
,5
]}

Zhang, Lu ^{[1
]}

Wong, Wilfred Hing Sang ^{[1
]}

Ng, Irene Oi Lin ^{[16
]}

Lau, Chak Sing ^{[10
]}

Sham, Pak Chung ^{[17
]}

Lau, Yu Lung ^{[1
]}

机构：

[1] Univ Hong Kong, LKS Fac Med, Dept Paediat & Adolescent Med, Pokfulam, Hong Kong, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Biol Sci, Joint Mol Rheumatol Lab, Inst Hlth Sci, Shanghai, Peoples R China

[3] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Renji Hosp, Shanghai, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China

[5] Anhui Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Hefei, Anhui, Peoples R China

[6] Shandong Univ, Sch Med, Dept Med Genet, Jinan 250100, Shandong, Peoples R China

[7] Shandong Univ, Sch Med, Key Lab Expt Teratol, Minist Educ, Jinan 250100, Shandong, Peoples R China

[8] Chulalongkorn Univ, Fac Med, Dept Microbiol, Lupus Res Unit, Bangkok 10330, Thailand

[9] Tuen Mun Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China

[10] Univ Hong Kong, LKS Fac Med, Dept Med, Pokfulam, Hong Kong, Peoples R China

[11] Pamela Youde Nethersole Eastern Hosp, Dept Med, Chaiwan, Hong Kong, Peoples R China

[12] Tuen Mun Hosp, Dept Paediat & Adolescent Med, Hong Kong, Hong Kong, Peoples R China

[13] Queen Elizabeth Hosp, Dept Med, Kowloon, Hong Kong, Peoples R China

[14] Anhui Prov Hosp, Dept Rheumatol, Hefei, Anhui, Peoples R China

[15] Chulalongkorn Univ, Fac Med, Dept Med, Bangkok 10330, Thailand

[16] Univ Hong Kong, LKS Fac Med, Dept Pathol, Pokfulam, Hong Kong, Peoples R China

[17] Univ Hong Kong, LKS Fac Med, Dept Psychiat, Pokfulam, Hong Kong, Peoples R China

来源：

PLOS GENETICS | 2010年 / 6卷 / 02期

基金：

中国国家自然科学基金; 国家高技术研究发展计划(863计划);

关键词：

HONG-KONG CHINESE; PLASMA-CELL DIFFERENTIATION; SUSCEPTIBILITY; GENE; DISEASE; ITGAM; RISK; POLYMORPHISM; ACTIVATION; NEPHRITIS;

D O I：

10.1371/journal.pgen.1000841

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33x10(-11), OR = 1.29; WDFY4: rs7097397, P = 8.15x10(-12), OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3'-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved.

引用

页数：11

共 52 条

[1] Single-nucleotide polymorphism analysis by pyrosequencing [J].

Ahmadian, A ;

Gharizadeh, B ;

Gustafsson, AC ;

Sterky, F ;

Nyrén, P ;

Uhlén, M ;

Lundeberg, J .

ANALYTICAL BIOCHEMISTRY, 2000, 280 (01) :103-110

[2] STUDIES IN FAMILIAL SYSTEMIC LUPUS-ERYTHEMATOSUS [J].

ARNETT, FC ;

SHULMAN, LE .

MEDICINE, 1976, 55 (04) :313-322

[3] Haploview: analysis and visualization of LD and haplotype maps [J].

Barrett, JC ;

Fry, B ;

Maller, J ;

Daly, MJ .

BIOINFORMATICS, 2005, 21 (02) :263-265

[4] Th17: the third member of the effector T cell trilogy [J].

Bettelli, Estelle ;

Korn, Thomas ;

Kuchroo, Vijay K. .

CURRENT OPINION IN IMMUNOLOGY, 2007, 19 (06) :652-657

[5] RECIPROCAL EXPRESSION OF HUMAN ETS1 AND ETS2 GENES DURING T-CELL ACTIVATION - REGULATORY ROLE FOR THE PROTOONCOGENE ETS1 [J].

BHAT, NK ;

THOMPSON, CB ;

LINDSTEN, T ;

JUNE, CH ;

FUJIWARA, S ;

KOIZUMI, S ;

FISHER, RJ ;

PAPAS, TS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (10) :3723-3727

[6] INCREASED T-CELL APOPTOSIS AND TERMINAL B-CELL DIFFERENTIATION-INDUCED BY INACTIVATION OF THE ETS-1 PROTOONCOGENE [J].

BORIES, JC ;

WILLERFORD, DM ;

GREVIN, D ;

DAVIDSON, L ;

CAMUS, A ;

MARTIN, P ;

STEHELIN, D ;

ALT, FW .

NATURE, 1995, 377 (6550) :635-638

[7] Association of BANK1 and TNFSF4 with systemic lupus erythematosus in Hong Kong Chinese [J].

Chang, Y. K. ;

Yang, W. ;

Zhao, M. ;

Mok, C. C. ;

Chan, T. M. ;

Wong, R. W. S. ;

Lee, K. W. ;

Mok, M. Y. ;

Wong, S. N. ;

Ng, I. O. L. ;

Lee, T. L. ;

Ho, M. H. K. ;

Lee, P. P. W. ;

Wong, W. H. S. ;

Lau, C. S. ;

Sham, P. C. ;

Lau, Y. L. .

GENES AND IMMUNITY, 2009, 10 (05) :414-420

[8]

CHEN J, 2009, AM J HUM GENET

[9] The biology of the Ets1 proto-oncogene [J].

Jürgen Dittmer .

Molecular Cancer, 2 (1)

[10] RETRACTED: Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus (Retracted Article) [J].

Doreau, Agnes ;

Belot, Alexandre ;

Bastid, Jeremy ;

Riche, Benjamin ;

Trescol-Biemont, Marie-Claude ;

Ranchin, Bruno ;

Fabien, Nicole ;

Cochat, Pierre ;

Pouteil-Noble, Claire ;

Trolliet, Pierre ;

Durieu, Isabelle ;

Tebib, Jacques ;

Kassai, Berhouz ;

Ansieau, Stephane ;

Puisieux, Alain ;

Eliaou, Jean-Francois ;

Bonnefoy-Berard, Nathalie .

NATURE IMMUNOLOGY, 2009, 10 (07) :778-U142

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